Treating alcohol dependence is a great unmet need worldwide. Developing medications to treat alcohol dependence is a high priority for the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and is currently one of 10 primary research outcome goals for the NIH. To fulfill this goal, NIAAA will implement a preclinical medication screening program (1) to foster discovery of lead compounds, targets and mechanisms, (2) to capitalize on the NIH Roadmap Molecular Libraries Initiative, and (3) to entice the pharmaceutical industry to develop their best marketable compounds for alcoholism treatment. During FY 2005, [unreadable]proof-of-principle[unreadable] tests were conducted to demonstrate the feasibility for successful testing using the clinically effective compounds naltrexone and acamprosate in rodent models of dispositional heavy drinking. We seek to implement contracts to test potential medications in heavy drinking paradigms which have demonstrated utility for medication screening during FY 2007. We will continue to test standard compounds to further validate the paradigms, and also begin testing compounds provided by pharmaceutical companies and individual investigators on a limited basis. We will use contractual mechanisms having intellectual property conditions favorable to compound providers. This will eliminate a major barrier to testing optimized compounds having preclinical as well as clinical toxicology data and will stimulate interest by the pharmaceutical industry in developing high quality, marketable compounds for alcoholism.